Reactive oxygen species-sensitive thioether-bearing poly(2-oxazoline)s: direct and controlled polymerization using an initiator salt

Abstract

Reactive oxygen species (ROS)-responsive polymers have attracted significant attention for their potential in biomedical applications, particularly in drug delivery and tissue engineering. This study presents the first direct synthesis and characterization of ROS-responsive thioether-bearing poly(2-oxazoline)s via controlled cationic ring-opening polymerization. Typical initiators have been shown to lead to loss of control over the polymerization of 2-(methylthio)-methyl-2-oxazoline. Here we show that its controlled polymerization is possible via the initiator salt method. The living character was confirmed by kinetic experiments and chain extension, used to synthesize amphiphilic block copolymers. Their ROS-responsiveness was evaluated through in vitro studies in the presence of hydrogen peroxide. The amphiphilic self-assemblies disassemble over time, as demonstrated for a triblock copolymer, suggesting a significant change of hydrophilicity of the polymer upon exposure to ROS. Together, the presented synthetic approach has much better atom economy than a previously published approach and enables facile and direct access to ROS-responsive POx with more complex architectures.